Biodegradation and Nanofunctionalization

Biodegradation of implant materials and medical product components

From a technological and regulatory perspective, innovative implants are among the most challenging medical products. Therefore, when it comes to selecting the implant material and the materials for medical product components, the critical minimum requirements must be analyzed first. The materials’ biodegradation is an important factor in this.

Tissue and body fluids come into contact with the implant surfaces. The interactions caused by this fact require detailed in-situ monitoring of the various phases of the degradation process. In the worst case, interactions result in the failure of the implant’s functions, decomposition or unwanted physical responses. Therefore, the Biodegradation and Nanofunctionalization workgroup investigates material changes and aging processes by using synthetic physiological media. The IKTS researchers develop innovative methods to analyze the biodegradation of various material classes and apply these methods.

The biodegradation analyses are accompanied by comprehensive characterization of physical-chemical material properties. The research and development efforts contribute to the optimal design of novel bioresorbable implants, such as stents, locating screws and bone substitute material. But optimization also extends to bioresorbable, drug-eluting implant coatings. The workgroup tries to determine the exact local and chronological process of degradation with regard to physiologically related environmental conditions (temperature, medium, mechanic stress). This enables manufacturers to influence the spatial original design and the manufacturing conditions of the degradable material or implant.

Functional nanostructures and nanoscale surface coatings

Research further focuses on the development of functional nanostructures, as well as wet-chemical thin-film methods, e.g. based on nanodiamonds (sp3 hybridized nanoscale carbon). Because several physical and chemical properties converge, such nanotechnological coatings have great synergistic effects. This translates into great potential for innovation for these knowledge fields in many areas of application, e.g. pharmacy, medical engineering or functional components.

The Biodegradation and Nanofunctionalization workgroup contributes to utilizing the innovation potential of nanomaterial-based developments in an economically profitable way. The IKTS researchers focus on functionalizing nano- and macroscopic materials, making biomaterials resistant to corrosive and abrasive wear, and on drug delivery technologies.

Ceramic-based microchips in biosensorics

Furthermore, the IKTS researchers develop approaches for ceramic-based biosensors, as well as the corresponding materials and processes for the manufacture and characterization of biosensors. High-performance ceramics play an increasing role in electronics, on account of the stability and reliability the technology has to offer. These advantages of ceramics are used for medical micro-electrochemical systems (MEMS), as well as for channel structures handling fluids and gases, even in extreme conditions. Also, integrated microelements made with functional ceramics provide more sensitivity and multiselectivity. Biosensors in particular can benefit from the well-known properties of ceramics, namely long-term stability, biocompatibility and the ability to combine electrical and insulating properties.

When developing high-performing biosensors, the immobilization of biomolecules is one of the core problems. The researchers focus on the long-term stability of the biosensor components, so as not to affect their stability, functionality and specificity. This is done under cyclic load, which can be functionalized biochemically if needed. To build the chips, various substrate materials for LTCC (low-temperature cofired ceramics) and gold pastes are selected. This selection of materials ensures optimal conditions for biosensoric application with the ceramic multilayer technique. This in turn will enable, in the future, 3D structuring and system integration while economically manufacturing larger quantities of hermetically sealed products.

Sensitive surface properties of gold contacts in biosensors

The use of electrodes in biosensors poses specific challenges regarding the surface properties of the gold contacts, and thus also to the ceramic substrate. Therefore, the roughness factor is optimized, i.e. decreased by 30 to 50 percent, depending on the LTCC. Through cyclic load testing in an acid medium, it was possible to identify suitable combinations which result in good adhesiveness and long-term stability of the gold contacts, as well as low decomposition and degradation values. Within these stationary ranges, it is possible to detect even weak signals under specific conditions. These signals occur when a target molecule docks onto a functionalized surface.

At the same time, the sensor design is optimized with the help of surface plasmon resonance spectroscopy (SPR). This shows that, in the detection of proteins through aptamer-functionalized gold surfaces, the signal is dependent on the concentration. LTCC biosensors modified using this knowledge can be used for in-vitro diagnostics or in biotechnology.

Services offered for biodegradation and nanofunctionalization

Biodegradation of implant materials and medical product components

• Physical-chemical in-vitro testing (including long-term testing) for biodegradation, biostability, decomposition and accumulation mechanisms
• Development of degradation models
• Electrochemical corrosion and degradation testing
• Integration testing of passivation layers on implants
• Assessment of the effect of various sterilization methods on the properties and functionality of implant materials
• Support in the selection of suitable sterilization methods

Nanofunctionalization and nanoscale surface coating

• Surface functionalization of macro- and nanoscale materials
• Integration of nanomaterials in bioscaffolds and coatings to improve bio- and haemocompatibility as well as mechanic properties
• Development and optimization of the liquid phase separation and electrochemical coating technology for medical products including the configuration of desired functions
• Analysis of complex colloidal media using spectroscopic approaches
• Development of low-molecular drug-nanomaterial conjugates (preclinical studies)
• Drug delivery: Characterization of drug-delivering systems with regard to the docking efficiency of the drugs, release kinetics and in-vitro cell reactions

Ceramic-based microchips in biosensorics

• Development of electrochemical ceramic-based sensors (assay development, biochemical sensor functionalization, biocompatible design and connection methods)
• Sensor measurement
• Biocompatible sensor packaging
• Sensor inspection and evaluation under the influence of media

Characterization of implant materials, medical product components and biosensors

• Examination of the topographic and morphological surface properties using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM/AFAM)
• IR and Raman spectroscopy, spectroscopic ellipsometry
• Surface plasmon resonance (SPR), Zetasizer nano-ZSP
• Static/dynamic coat thickness measurement
• Fluid-dynamic measurements
• Potentiostatic testing
• Measurements of clean-room conditions (ISO-2)

Selected projects and cooperative research initiatives

• Eurostars project "Biostar 17":
  Enables scientific cooperation between Fraunhofer IKTS and partners from the industry, BioCopy (Germany), InnoPharmaScreen Inc. (Korea) and NeoVentures (Canada), as well as the Asan Clinic in Korea. The cooperative research project focuses on the development of an aptamer-based biosensor for the ALK-based therapy of non-small-cell lung cancer.
• Fraunhofer project "DeZeMag":
  The project aims to develop an innovative polymer-ceramic degradation layer whose bioresorptive properties can be time-controlled, for coronary magnesium stents.
• Era.Net.Rus.Plus project "TiOxTechBio":
  Cooperative research project between Fraunhofer IKTS and Balton Ltd. (Poland), VIP Technologies Ltd. (Russian Federation) as well as the POLITECHNICA University, Bucharest, with the aim of developing titanium oxide nitride coatings to improve the biostability and long-term functionality of cardiovascular stents.
• Ph.D. thesis project "Surface engineering of Ti-based materials using detonation nanodiamonds":
  Proof of concept and development of a nanodiamond-based coating system for biomedical applications. The Ph.D. thesis is part of the International Excellence Graduate School on Emerging Materials and Processes (iEGSEMP Korea).